Premium
A hybrid method of molecular dynamics and harmonic dynamics for docking of flexible ligand to flexible receptor
Author(s) -
Tatsumi Rie,
Fukunishi Yoshifumi,
Nakamura Haruki
Publication year - 2004
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.20133
Subject(s) - docking (animal) , molecular dynamics , searching the conformational space for docking , chemistry , computational chemistry , biological system , chemical physics , binding site , biology , biochemistry , medicine , nursing
We have developed a new docking method to consider receptor flexibility, a hybrid method of molecular dynamics and harmonic dynamics. The global motions of the whole receptor were approximately introduced into those of the receptor in the docking simulation as harmonic dynamics. On the other hand, the local flexibility of the side chains was also considered by conventional molecular dynamics. We confirmed that this new method can reproduce the fluctuations of the whole receptor by making a comparison of the directions and amplitudes of the global fluctuations. Then this method was applied to the docking of HIV‐1 protease and its ligand. As a result, we observed a docking process where the ligand enters into the binding pocket well, which implies that this method is effective enough to reproduce a molecular complex formation. © 2004 Wiley Periodicals, Inc. J Comput Chem 25: 1995–2005, 2004